Is COL28A1 p.Pro390Ser (c.1168C>T) pathogenic?

COL28A1 p.Pro390Ser (c.1168C>T) is classified Uncertain significance in COL28A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0995); Absent from gnomAD v4.1.

How common is COL28A1 p.Pro390Ser (c.1168C>T) in the general population?

COL28A1 p.Pro390Ser (c.1168C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL28A1 p.Pro390Ser (c.1168C>T)?

AlphaMissense predicts likely benign (score 0.0995) — an in-silico prediction, not a clinical call.

COL28A1 p.Pro390Ser

c.1168C>T · VCV4655616

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0995 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,222,714)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0995	likely benign
REVEL	0.535	indeterminate
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.8, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 174 kb · p 8.4e-10 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,222,714). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL28A1
Protein: p.Pro390Ser
Coding: c.1168C>T
MANE Select: NM_001037763
Type: single nucleotide variant
Location: chr7:7477177 (GRCh38)
Gene constraint: LOEUF 1.124 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.81
Residue 390: the 'disordered' region; the collagen-like 3 domain

Full COL28A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL28A1 c.1792-2A>G Uncertain significance ★ same type
COL28A1 p.Ala1075Asp Uncertain significance ★ ⚠ same type
COL28A1 p.Ala274Thr Uncertain significance ★ ⚠ same type
COL28A1 p.Ala535Gly Uncertain significance ★ ⚠ same type
COL28A1 p.Ala631Asp Uncertain significance ★ ⚠ same type
COL28A1 p.Ala825Val Uncertain significance ★ ⚠ same type
COL28A1 p.Ala864Ser Uncertain significance ★ ⚠ same type
COL28A1 p.Arg1087Gln Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/col28a1-p-pro390ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown